THE EFFECT OF WHOLE-BODY IRRADIATION OF NUDE-MICE ON THE TUMOR TRANSPLANTABILITY AND CONTROL PROBABILITY OF A HUMAN SOFT-TISSUE SARCOMA XENOGRAFT

This study has evaluated the impact of the suppression and recovery of the residual immunity in NCr/Sed nude (nu/nu) mice after whole-body i rradiation using xenotransplantability and tumor control probability a s the end points. For this investigation the xenograft was a human sof t tissue sarcoma (HSTS26T). Two assays, the TD50 (the number of tumor cells required to induce a tumor in 50% of the recipients) and the TCD 50 (the radiation dose required to control 50% of tumors) were used. F or TD50 assays, tumor cells were injected subcutaneously (sc) into the legs of control and whole-body-irradiated nude mice at 1 day or 4, 8 or 12 weeks after irradiation. For TCD50 assays, tumors were transplan ted sc into the legs of nude mice which had not been irradiated or whi ch had been given whole-body irradiation at 1 day or 12 weeks prior to transplantation. The tumors were given single-dose irradiation when t hey reached 6 mm mean diameter under clamp-hypoxic conditions. The res ults show that the TD50's of mice receiving the injection 1 day and 4 and 8 weeks after whole-body irradiation were 3.6 to >100 times lower than that of unirradiated mice. Two groups which showed a statisticall y significant difference in TD50's were those which received the injec tion 1 day and 8 weeks after whole-body irradiation (P < 0.01 and P < 0.05, respectively). No difference was found in TD50 values between mi ce that received injection 12 weeks after whole-body irradiation and t hose which were not irradiated. The TCD50 values of tumors in nonirrad iated mice and in mice which had received whole-body irradiation 1 day and 12 weeks prior to transplantation were 26.8, 44.1 and 33.9 Gy, re spectively, Significantly lower TCD50 values were found in groups of n onirradiated mice or mice which received whole-body irradiation 12 wee ks prior to transplantation in comparison with the group of mice that received whole-body irradiation on day 1 (both P < 0.05). No significa nt difference was found between the TCD50 values of the group of mice that received whole-body irradiation 12 weeks prior to transplantation and those for nonirradiated controls. Our conclusion is that the whol e-body irradiation can enhance the transplantability of the HSTS26T tu mor in nude mice significantly; this enhancing effect will decrease to the pre-irradiation level by 12 weeks after whole-body irradiation. A lso, the suppression and recovery of residual immunity after whole-bod y irradiation can influence the TCD50 values of the same tumor xenogra fts in nude mice significantly. The changes in TD50 and TCD50 values c orrelate with the depletion and recovery of the total splenic lymphoid cell number, and especially in natural killer cell activity. We recom mend that further immunosuppression in nude mice is necessary when usi ng this model system for studies of human tumors. (C) 1996 by Radiatio n Research Society